Switch Maintenance With Paclitaxel, Ramucirumab for HER2-Negative Metastatic Gastric/GEJ Cancers

At the 2024 American Society of Clinical Oncology Annual Meeting, Filippo Pietrantonio, MD, presented results of the phase 3 ARMANI trial that examined ramucirumab with paclitaxel as switch maintenance therapy versus the continuation of oxaliplatin-based chemotherapy in patients with advanced HER2-negative gastric or gastroesophageal junction (GEJ) cancers.

Platinum and fluoropyrimidine doublet combinations are a standard first-line therapy for patients with HER2-negative advanced gastric/GEJ cancers and PD-1 low and absent expression; however, patient outcomes are often unsatisfactory, and second-line therapy is used in only 40% of clinical trial patients.

Switch maintenance may extend the benefit of the initial treatment strategy and can delay clinical deterioration. While ramucirumab has failed to prolong progression-free survival (PFS) and overall survival (OS) in the first-line setting, combining the treatment with paclitaxel is a second-line therapy that warrants investigation as a postinduction strategy.

From January 2017 to October 2023, 280 patients were randomized to receive ramucirumab 8 mg/kg on days 1 and 15 plus paclitaxel 80 mg/sqm on days 1, 8, and 15 every 28 days (arm A, 144 patients) or capecitabine and oxaliplatin and 5-fluorouracil, leucovorin, and oxaliplatin (CAPOX/FOLFOX) at the same doses used in the last induction cycle for an additional 3 months, followed by fluoropyrimidine monotherapy maintenance (arm B, 136 patients).

The primary end point was PFS, with OS as a key secondary end point. A total of 74 (65%) patients had a performance status of 0, 26 (26%) had GEJ, 28 (23%) had prior gastrectomy, and 53 (42%) had peritoneal metastases.

At a median follow-up of 43.7 months (IQR, 22.0-57.9), the median PFS was 6.6 and 3.5 months in arms A and B (hazard ratio [HR], 0.63; 95% CI, 0.49-0.81; P<.001), respectively. The median OS was 12.6 in arm A and 10.4 months in arm B (HR, 0.75; 95% CI, 0.58-0.97; P=.030). A 24-month restricted mean survival time analysis showed a statistically significant 2.4-month average increment (P=.002).

Grade ≥3 adverse events, including neutropenia, febrile neutropenia, and hypertension, occurred in 40.4% and 20.7% of patients in arms A and B, respectively. No treatment-related deaths were reported.

Switch maintenance using paclitaxel and ramucirumab after 3 months of oxaliplatin-based chemotherapy doublets can serve as a new treatment strategy for patients with HER2-negative metastatic gastric/GEJ cancers who are noneligible for initial immune checkpoint inhibitor-based therapies.